Advanced or metastatic breast cancer with ErbB2 FISH postive tumours
Conditions
Interventions
Product Name: Pazopanib
Product Code: GW786034B
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Pazopanib
CAS Number: 63570
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women >18 years of age with a life expectancy of >12 weeks. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 3. Histologically confirmed invasive breast cancer with incurable stage IIIb, stage IIIc with T4 lesion, or stage IV disease at primary diagnosis or at relapse after curative-intent surgery. 4. Documented amplification of ErbB2 by FISH in either the primary or metastatic tumor tissue. Archived tumor tissue must be provided for ErbB2 FISH testing by the central laboratory, which will be used to determine eligibility. Note: Subjects that have documented ErbB2 amplification based on prior FISH testing or documented ErbB2 overexpression based on prior immunohistochemistry (ICH) with a value of 3+ are eligible, however, archived tumor tissue must be provided for re-confirmation by the central laboratory. If the results from the central laboratory are unconfirmed, then the subject can continue to receive study drug(s) at the discretion of the investigator, but will be excluded from the statistical analysis and replaced. 5. Disease must be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST). 6. No prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic or recurrent disease (other than neoadjuvant or adjuvant therapy). Prior hormonal therapy (e.g., tamoxifen, raloxifen or an aromatase inhibitor) for advanced or metastatic disease is permitted provided at least 2 weeks have elapsed between the completion of the prior therapy and start of study drugs. 7. Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive or where MUGA scans are the accepted standard. Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or antiseizure medication for >2 months prior to study enrollment. Routine screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases. 2. Sarcoma histology 3. Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, and tumor embolization). 4. Concurrent treatment with an investigational agent or participation in another clinical trial. 5. Use of an investigational anti-cancer drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of pazopanib and/or lapatinib. 6. Prior use of an investigational or licensed drug that targets either VEGF or VEGF receptors, or ErbB2 (except for trastuzumab when used in the neo-adjuvant/adjuvant setting).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the rate of disease progression at 12 weeks between pazopanib (400 mg) in combination with lapatinib (1000 mg) versus lapatinib alone (1500 mg) in subjects randomised in cohort 1 with locally advanced or metastatic breast cancer whose tumors are ErbB2 FISH+.; Secondary Objective: The principal secondary objective is to evaluate the week 12 response rate in subjects receiving the higher combination dose (cohort 2 - pazopanib 800 mg and lapatinib 1500 mg). Other secondary objectives include evaluation of response rate at week 12 in cohort 1, rate of disease progression at week 12 in cohort 2, overall survival, time to response, duration of response, safety and tolerability. ;Primary end point(s): 12-week Progressive Disease Rate defined as the percentage of subjects within each group in cohort 1 with progressive disease 12 weeks after randomization. This endpoint will be assessed at both the interim and final analyses. | — |
Countries
Hungary, United Kingdom
Outcome results
None listed